Nutritional compositions

ABSTRACT

In some aspects, the disclosure relates to compositions useful for the dietary management of inborn errors of metabolism (e.g., PKU, MSUD, HCU, IVA, and MMA/PA). In some embodiments, the disclosure provides a composition comprising a protein source, a fat source, a carbohydrate source, at least one vitamin, and at least one mineral, wherein the protein source comprises at least six free amino acids. In some aspects the disclosure relates to compositions that support bone health.

RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. 119(e) of U.S.provisional patent application U.S. Ser. No. 62/188,208, filed on Jul.2, 2015, entitled “Nutritional Compositions”, and U.S. provisionalpatent application U.S. Ser. No. 62/189,145, filed on Jul. 6, 2016,entitled “Nutritional Compositions.” The teachings of both applicationsare incorporated by reference herein.

BACKGROUND OF INVENTION

Inborn errors of metabolism are a group of inherited disorderscharacterized by defective function of one or more metabolic enzymes.Several inborn errors of metabolism are related to enzymes thatmetabolize amino acids. In these disorders, a lack of enzymatic activitycauses an inability to fully metabolize proteins or peptides, leading toan accumulation of toxic byproducts and reduced ability to synthesizeessential compounds. For example, Phenylketonuria (PKU) is caused by amutation that reduces or abrogates activity of the phenylalaninehydroxylase (PAH) gene. Impaired metabolism leads to a toxic buildup ofphenylalanine (Phe) in the brain, resulting in intellectual disabilityand seizures. Inborn errors of metabolism are also often related tosecondary medical issues, such as low bone mineral density.

Inborn errors of metabolism related to amino acid metabolism can bemanaged by a controlled diet that reduces or excludes the amino acidthat the patient is unable to break down (e.g., a diet lacking or low inPhe for a PKU patient). Generally, the protein source provided by thesediets is a mixture of elemental amino acids. Controlled diets can beadministered in the form of nutritional formulas, which can bereconstituted from powdered mixes or provided in a ready to drink (RTD)liquid format. However, patient compliance with controlled diets basedon nutritional formulas is an issue, with some patients citingunacceptable taste of nutritional formulas as a reason fornon-compliance.

Accordingly, there is a need to develop novel nutritional formulashaving acceptable palatability and improved nutrient profiles for thedietary management of inborn errors of metabolism.

SUMMARY OF INVENTION

Described herein are compositions (e.g., amino acid-based formulas) thatare useful for the dietary management of inborn errors of metabolism. Insome embodiments, the compositions are nutritionally complete, supportpatient bone health and have an acceptable taste.

In some aspects, the disclosure relates to compositions for the supportof bone health (bone health composition) in patients with inborn errorsof metabolism. Bone health compositions can be solid (e.g., a powder) orliquid. In some embodiments, bone health compositions comprise VitaminD, calcium, phosphorus, zinc, magnesium, and Vitamin K. In someembodiments, Vitamin K is a combination of Vitamin K1 and Vitamin K2. Insome embodiments, equal amounts (e.g., by gram weight) of Vitamin K1 andVitamin K2 are present in the composition. In some embodiments, bonehealth compositions further comprise a dietary fiber. In someembodiments, the dietary fiber is inulin.

The amount of each component in a bone health composition can beexpressed as a percentage of the total weight of the bone healthcomposition or as the weight of each component in the amount of bonehealth composition that is included per serving of nutritionalcomposition. Typically the amount of bone health composition is fromabout 1.5 g to about 4.0 g per serving. The percentage of bone healthblend in a total serving ranges from about 0.43 to about 0.68. In someembodiments, bone health compositions further comprise a protein sourceand the amount of each component in the composition is expressed asweight per g protein equivalent (PE) (e.g., per 20 g PE). In someembodiments, a protein source comprises one or more amino acids selectedfrom the group consisting of: histidine, isoleucine, leucine, lysine,methionine, phenylalanine, threonine, tryptophan, and valine. Examplesof ranges for each component of a bone health composition are describedin Table 1. In some embodiments, a bone health composition is acomponent in a vitamin and mineral mixture, for example as shown inTable 2 or Table 7.

In some aspects, the disclosure provides nutritional compositions fordietary management of inborn errors of metabolism comprising componentsdescribed herein. The inborn error of metabolism can be Phenylketonuria(PKU), Maple Syrup Urine Disease (MSUD), Homocystinuria (HCU),Isovaleric acidaemia (IVA), and Methylmalonic acidaemia/Propionicacidaemia (MMA/PA). In some embodiments, nutritional compositionscomprise a protein source, a fat source, a carbohydrate source, the bonehealth composition, wherein the protein source comprises at least sixfree amino acids. The nutritional compositions are liquids and in someembodiments, the pH of a nutritional composition is between about pH 5.0and about pH 6.0.

In some embodiments, the at least six free amino acids are selected fromthe group consisting of: histidine, isoleucine, leucine, methionine,phenylalanine, threonine, tryptophan, and valine. In some embodiments,nutritional compositions further comprise at least one amino acidselected from the group consisting of glycine, alanine, arginine,asparagine, aspartic acid, cystine, glutamic acid, glutamine, proline,serine, and tyrosine. In some embodiments, the protein source is amixture of amino acids (e.g., a blend of amino acids), for example asshown in Table 4 or Table 10.

The amount of each amino acid in a nutritional composition can beexpressed as weight per g protein equivalent (PE) (e.g., per 20 g PE),or as weight of each component per serving. In some embodiments, aserving of liquid nutritional composition is about 8.5 fluid oz (i.e.,about 250 mL).

The liquid nutritional formula may contain additional components, forexample carnitine, taurine, Docosahexaenoic acid (DHA), alone or incombination (e.g., carnitine and taurine; carnitine, taurine, and DHA;carnitine and DHA; or taurine and DHA).

In some embodiments, the nutritional composition comprises: Vitamin A,Vitamin D, Vitamin E, biotin, folic acid, niacin, pantothenic acid,Vitamin B1, Vitamin B12, Vitamin B2, Vitamin B6, Vitamin C, and VitaminK and calcium, chromium, copper, iodine, iron, magnesium, manganese,molybdenum, phosphorus, potassium, selenium, sodium, and zinc. In someembodiments, the nutritional composition includes a vitamin and mineralblend, for example as represented in Table 2 or Table 7. The amount ofeach vitamin or mineral in a nutritional composition for dietarymanagement of inborn errors of metabolism can be expressed as apercentage of the total weight of the composition, the weight of eachvitamin or mineral per serving, or the weight of each vitamin or mineralper g PE (e.g., per 20 g PE).

In some aspects, the disclosure relates to a nutritional composition fordietary management of an inborn error of metabolism, comprising thecomponents set forth in Table 5. In some embodiments, the amino acidblend is selected from the blends in Table 4 or Table 10. In someembodiments, the amino acid blend is selected from the group consistingof Blend 1, Blend 2, Blend 3, Blend 4 or Blend 5 in Table 4, and Blend1, Blend 2, Blend 3, Blend 4 or Blend 5 in Table 10. In someembodiments, a nutritional composition for dietary management of aninborn error of metabolism provides (per 8.5 fluid oz.) about 15, about16 g PE, about 17 g PE, about 18 g PE, about 19 g PE, about 20 g PE, orabout 21 g PE.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows non-limiting embodiments of nutritional compositions fordietary management of inborn errors of metabolism comprising componentsdescribed by the disclosure.

OPTIMIZED PROFILE FEATURES AND BENEFITS

-   -   Nutritionally complete plus EFAs—so you are meeting not just        their protein needs    -   20 g PE/serving—a concentrated source of protein to help with        adherence    -   Bone Health Blend optimized to promote bone health:    -   Per serving:        -   Vitamin D 620 IU—highest level compared to other AA formulas        -   Calcium 700 mg        -   Phosphorus 695 mg        -   Zn 5 mg        -   Mg 160 mg        -   Vitamin K (K1, K2) 40 mcg, levels optimized for bone health¹        -   Inulin 2 g, to aid in calcium absorption² (excludes            Promactin)        -   DHA 150 mg/serving—to support brain and eye development        -   3 g Pre-biotic fiber/serving to support digestive health            (excludes Promactin)        -   pH 5.8, Lower acidity than other AA formulas—gentler on            digestion and overall milder taste        -   Great tasting Berry flavor—smooth taste unlike other AA RTD            products        -   No artificial flavoring or coloring—requested by you and            your patients        -   Convenient ready to drink—making it easy to fit into your            busy life FOR A SAMPLE call 866 456 9776, opt 2 or complete            the online form: www.samples.cambrooke.com    -   CAMBROOKEcare™    -   CAMBROOKEcare is available to anyone needing assistance with:    -   low protein food coverage support    -   metabolic formula coverage support    -   coverage assistance support services    -   co-pay assistance    -   coding and billing information for patients and healthcare        providers    -   insurance direct billing services    -   supplier sourcing (pharmacy, durable medical equipment [DME],        etc. . . . )    -   CONTACT OUR COVERAGE SPECIALISTS:    -   866 383 9455    -   reimbursement@cambrooke.com    -   CAMBROOKEcare™ is a full service coverage and reimbursement        assistance program offered through Cambrooke Therapeutics™

REFERENCES

-   1. Marieke J, et al. (2008). Vitamin K status is associated with    childhood bone mineral content. British Journal of Nutrition, 100,    852-858.-   2. Scholz-Ahrens, K, Schrezenmeir, J. Inulin, oligofructose and    mineral metabolism—experimental data and mechanism.-   CAMBROOKEcare™ 866 383 9455 reimbursement@cambrooke.com    cambrookecare.com, © Cambrooke Therapeutics, Inc. All Rights    Reserved R062515

FIG. 2 shows non-limiting embodiments of nutritional compositions fordietary management of inborn errors of metabolism comprising componentsdescribed by the disclosure.

OPTIMIZED PROFILE FEATURES AND BENEFITS

-   -   Nutritionally complete plus EFAs—so you are meeting not just        their protein needs    -   20 g PE/serving—a concentrated source of protein to help with        adherence    -   Bone Health Blend optimized to promote bone health:    -   Per serving:        -   Vitamin D 620 IU—highest level compared to other AA formulas        -   Calcium 700 mg        -   Phosphorus 695 mg        -   Zn 5 mg        -   Mg 160 mg        -   Vitamin K (K1, K2) 40 mcg, levels optimized for bone health′        -   Inulin 2 g, to aid in calcium absorption² (excludes            Promactin)    -   DHA 150 mg/serving—to support brain and eye development    -   3 g Pre-biotic fiber/serving to support digestive health        (excludes Promactin)    -   pH 5.8, Lower acidity than other AA formulas—gentler on        digestion and overall milder taste    -   Great tasting Berry flavor—smooth taste unlike other AA RTD        products    -   No artificial flavoring or coloring—requested by you and your        patients    -   Convenient ready to drink—making it easy to fit into your busy        life    -   FOR A SAMPLE    -   call 866 456 9776, opt 2 or complete the online form:    -   www.samples.cambrooke.com    -   CAMBROOKEcare™    -   CAMBROOKEcare is available to anyone needing assistance with:        -   low protein food coverage support        -   metabolic formula coverage support        -   coverage assistance support services        -   co-pay assistance        -   coding and billing information for patients and healthcare            providers        -   insurance direct billing services        -   supplier sourcing (pharmacy, durable medical equipment            [DME], etc. . . . )    -   CONTACT OUR COVERAGE SPECIALISTS:    -   866 383 9455    -   reimbursement@cambrooke.com    -   CAMBROOKEcare™ is a full service coverage and reimbursement        assistance program offered through Cambrooke Therapeutics™

REFERENCES

-   1. Marieke J, et al. (2008). Vitamin K status is associated with    childhood bone mineral content. British Journal of Nutrition, 100,    852-858.-   2. Scholz-Ahrens, K, Schrezenmeir, J. Inulin, oligofructose and    mineral metabolism—experimental data and mechanism.-   CAMBROOKEcare™ 866 383 9455 reimbursement@cambrooke.com    cambrookecare.com-   © Cambrooke Therapeutics, Inc. All Rights Reserved R062515

FIG. 3 shows a non-limiting embodiment of a product label for anutritional composition for dietary management of Homocystinurea (HCU).

SKU 37001

NET WEIGHT 2 GAL (7.5 L)

SERVING SIZE 8.5 fl oz (250 mL)

SERVINGS PER PACKAGE 30

REIMBURSEMENT CODE 24359-0701-03 (for USA only)

MEDICAL FOOD PRODUCT

For the dietary management of Homocystinurea (HCU). Dispensed byprescription. Homactin AA Plus is a ready-to-drink metabolic formulaproduct for Homocystinurea patients, over 1 year of age. Homactincontains an advanced fortification blend. Product comes in a 250 mLcarton.PRECAUTIONS For the dietary management of Homocystinuria (HCU). Use asdirected by physician. Must be administered under medical supervisiononly.

NOT FOR PARENTERAL USE•USE AS DIRECTED BY PHYSICIAN INGREDIENTS

Water, amino acid blend (L-leucine, L-aspartic, L-proline, L-lysine HCl,L-valine, L-arginine, glycine, L-isoleucine, L-tyrosine, L-serine,L-threonine, L-phenylalanine, L-alanine, L-histidine, L-cystine,L-tryptophan, taurine, L-carnitine, maltodextrin), vitamins and minerals(calcium lactate, monosodium phosphate, monopotassium phosphate, cholinebitartrate, magnesium amino acid chelate, sodium ascorbate, ascorbicacid, dl-alpha-tocopheryl acetate, Fe amino acid chelate, niacinamide,zinc amino acid chelate, calcium d-pantothenate, manganese sulfate,riboflavin, B6 Pyrodixine HCl, thiamin HCl, copper gluconate, folicacid, vitamin A palmitate, potassium iodide, sodium selenite,cholecalciferol, K1 phytonadione, K2 MK-7, sodium molybdate,cholecalciferol, chromium chloride, biotin, B12 cyanocobalamin), canolaoil, sugar, natural flavors (propylene glycol, water, potassiumsorbate), inulin, cellulose gel and carboxymethylcellulose sodium, foodstarch modified, sodium hexametaphosphate, DHA algal oil, acesulfamepotassium, carrageenan, sucralose. Contains corn and soy.

PREPARATION

Ready to drink. Shake well.

STORAGE

Store in cool, dry place. Refrigerate after opening. Do not freeze.

TO REQUEST A SAMPLE

Call 866 456 9776, opt 2 or complete form: www.samples.cambrooke.com

HOMACTIN AA PLUS

Nutrients 8.5 fl oz (250 mL) Per 100 mL Calories 186 74 Calories FromFat 57 23 Protein Equivalent, g 20 8 Free Amino Acids, g 23 9Carbohydrates, g 13 5 Sugar, g 5 2 Sugar Alcohols, g 0 0 Dietary Fiber,g 2.8 1 Fat, g 6 2.4 Saturated Fat, g 0.5 0.2 Trans Fat, g 0.0 0.0 DHA,mg 150.0 60.0 Cholesterol, mg 0.4 0 Vitamin A, IU 1100.0 440.0 VitaminC, mg 40.0 16.0 Vitamin D, IU 620.0 248.0 Vitamin E, IU 10.0 4.0 VitaminK1, mcg 20.0 8.0 Vitamin K2 (MK-7), mcg 20.0 8.0 Thiamin (B1), mg 0.50.2 Riboflavin (B2), mg 0.5 0.2 Niacin (B3), mg 6.6 2.6 Vitamin B6, mg0.5 0.2 Folic Acid, mcg 186.0 74.4 Vitamin B12, mcg 1.0 0.4 PantothenicAcid (B5), mg 2.4 1.0 Biotin, mcg 10.6 4.2 Choline, mg 209.0 83.6Calcium, mg 677.0 270.8 Chromium, mcg 17.3 6.9 Copper, mg 0.2 0.1Iodine, mcg 76.0 30.4 Iron, mg 8.0 3.2 Magnesium, mg 143.0 57.2Manganese, mg 1.0 0.4 Molybdenum, mcg 20.0 8.0 Phosphorus, mg 664.0265.6 Selenium, mcg 26.6 10.6 Zinc, mg 5.0 2.0 Potassium, mg 573.0 229.2Sodium, mg 287.0 114.8 Chloride, mg 463.0 185.2 Inositol, mg 0.0 0.0L-alanine, mg 1070.0 428.0 L-arginine, mg 1550.0 620.0 L-asparagine, mg0.0 0.0 L-aspartate, mg 1930.0 772.0 L-carnitine, mg 21.0 8.4 L-cystine,mg 393.2 157.3 L-glutamate, mg 0.0 0.0 L-glycine, mg 1500.0 600.0L-histidine, mg 930.0 372.0 L-isoleucine, mg 1430.0 572.0 L-leucine, mg2450.0 980.0 L-lysine, mg 1620.0 648.0 L-methionine, mg 0.0 0.0L-phenylalanine, mg 1080.0 432.0 L-proline, mg 1760.0 704.0 L-serine, mg1250.0 500.0 L-taurine, mg 50.0 20.0 L-threonine, mg 1140.0 456.0L-tryptophan, mg 480.0 192.0 L-tyrosine, mg 786.4 314.6 L-valine, mg1560.0 624.0

FIG. 4 shows a non-limiting embodiment of a product label for anutritional composition for dietary management of Isovaleric Acidemia(IVA).

SKU 37002

NET WEIGHT 2 GAL (7.5 L)

SERVING SIZE 8.5 fl oz (250 mL)

SERVINGS PER PACKAGE 30

REIMBURSEMENT CODE 24359-0702-03 (for USA only)

MEDICAL FOOD PRODUCT

For the dietary management of Isovaleric Acidemia. Dispensed byprescription. Isovactin AA Plus is a ready-to-drink metabolic formulaproduct for Isovaleric Acidemia patients, over 1 year of age. Isovactincontains an advanced fortification blend. Product comes in a 250 mLcarton.PRECAUTIONS For the dietary management of Isovaleric Acidemia (IVA) andother disorders of leucine metabolism. Use as directed by physician.Must be administered under medical supervision only.

NOT FOR PARENTERAL USE•USE AS DIRECTED BY PHYSICIAN INGREDIENTS

Water, amino acid blend (L-alanine, glycine, L-proline, L-arginine,L-lysine, L-tyrosine, L-phenylalanine, L-serine, L-carnitine, L-asparticacid, L-threonine, L-valine, L-isoleucine, L-histidine, L-menthionine,L-tryptophan, L-cystine, taurine), vitamins and minerals (calciumlactate, monosodium phosphate, monopotassium phosphate, cholinebitartrate, magnesium amino acid chelate, sodium ascorbate, ascorbicacid, dl-alpha-tocopheryl acetate, Fe amino acid chelate, niacinamide,zinc amino acid chelate, calcium d-pantothenate, manganese sulfate,riboflavin, B6 Pyridoxal 5′ Phosphate, thiamin HCl, copper gluconate,L-methylfolate, vitamin A palmitate, potassium iodide, sodium selenite,cholecalciferol, K1 phytonadione, K2 MK-7, sodium molybdate,cholecalciferol, chromium chloride, biotin, B12 methylcobalamin), canolaoil, sugar, natural flavors (propylene glycol, water, potassiumsorbate), inulin, cellulose gel and carboxymethylcellulose sodium, foodstarch modified, sodium hexametaphosphate, DHA algal oil, acesulfamepotassium, carrageenan, sucralose. Contains corn and soy.

PREPARATION

Ready to drink. Shake well.

STORAGE

Store in cool, dry place. Refrigerate after opening. Do not freeze.

TO REQUEST A SAMPLE

Call 866 456 9776, opt 2 or complete form: www.samples.cambrooke.com

ISOVACTIN AA PLUS

Nutrients 8.5 fl oz (250 mL) Per 100 mL Calories 186 74 Calories FromFat 57 23 Protein Equivalent, g 20 8 Free Amino Acids, g 22 9Carbohydrates, g 13 5 Sugar, g 5 2 Sugar Alcohols, g 0 0 Dietary Fiber,g 2.8 1 Fat, g 6 2.4 Saturated Fat, g 0.5 0.2 Trans Fat, g 0.0 0.0 DHA,mg 150.0 60.0 Cholesterol, mg 0.4 0 Vitamin A, IU 1100.0 440.0 VitaminC, mg 40.0 16.0 Vitamin D, IU 620.0 248.0 Vitamin E, IU 10.0 4.0 VitaminK1, mcg 20.0 8.0 Vitamin K2 (MK-7), mcg 20.0 8.0 Thiamin (B1), mg 0.50.2 Riboflavin (B2), mg 0.5 0.2 Niacin (B3), mg 6.6 2.6 Vitamin B6, mg0.5 0.2 Folic Acid, mcg 186.0 74.4 Vitamin B12, mcg 1.0 0.4 PantothenicAcid (B5), mg 2.4 1.0 Biotin, mcg 10.6 4.2 Choline, mg 209.0 83.6Calcium, mg 677.0 270.8 Chromium, mcg 17.3 6.9 Copper, mg 0.2 0.1Iodine, mcg 76.0 30.4 Iron, mg 8.0 3.2 Magnesium, mg 143.0 57.2Manganese, mg 1.0 0.4 Molybdenum, mcg 20.0 8.0 Phosphorus, mg 664.0265.6 Selenium, mcg 26.6 10.6 Zinc, mg 5.0 2.0 Potassium, mg 573.0 229.2Sodium, mg 287.0 114.8 Chloride, mg 358.0 143.2 Inositol, mg 0.0 0.0L-alanine, mg 4340.0 1736.0 L-arginine, mg 1900.0 760.0 L-asparagine, mg0.0 0.0 L-aspartate, mg 1110.0 444.0 L-carnitine, mg 1130.0 452.0L-cystine, mg 161.9 64.8 L-glutamate, mg 0.0 0.0 L-glycine, mg 2180.0872.0 L-histidine, mg 600.0 240.0 L-isoleucine, mg 630.0 252.0L-leucine, mg 0.0 0.0 L-lysine, mg 1440.0 576.0 L-methionine, mg 431.0172.4 L-phenylalanine, mg 1230.0 492.0 L-proline, mg 2150.0 860.0L-serine, mg 1160.0 464.0 L-taurine, mg 43.0 17.2 L-threonine, mg 1050.0420.0 L-tryptophan, mg 229.0 91.6 L-tyrosine, mg 994.6 397.8 L-valine,mg 717.0 286.8

FIG. 5 shows a non-limiting embodiment of a product label for anutritional composition for dietary management of Phenylketonuria (PKU).

SKU 37005

NET WEIGHT 2 GAL (7.5 L)

SERVING SIZE 8.5 fl oz (250 mL)

SERVINGS PER PACKAGE 30

REIMBURSEMENT CODE 24359-0705-03 (for USA only)

MEDICAL FOOD PRODUCT

For the dietary management of Phenylketonuria (PKU). Dispensed byprescription. Phenactin AA Plus is a ready-to-drink metabolic formulaproduct for PKU patients, over 1 year of age. Phenactin Plus contains anadvanced fortification blend. Product comes in a 250 mL carton.PRECAUTIONS Give only to adults and children who are under medicalsupervision for proven PKU. Protein in prescribed amounts must besupplemented to completely meet phenylalanine requirements.

NOT FOR PARENTERAL USE•USE AS DIRECTED BY PHYSICIAN INGREDIENTS

Water, amino acid blend (L-leucine, L-tyrosine, L-lysine HCl, L-valine,L-aspartic, L-proline, L-threonine, L-isoleucine, L-serine, L-arginine,L-histidine, L-cystine, glycine, L-methionine, L-tryptophan, L-alanine,taurine, L-carnitine, maltodextrin), vitamins and minerals (calciumlactate, monosodium phosphate, monopotassium phosphate, cholinebitartrate, magnesium amino acid chelate, sodium ascorbate, ascorbicacid, dl-alpha-tocopheryl acetate, Fe amino acid chelate, niacinamide,zinc amino acid chelate, calcium d-pantothenate, manganese sulfate,riboflavin, B6 pyridoxine HCl, thiamin HCl, copper gluconate, folicacid, vitamin A palmitate, potassium iodide, sodium selenite,cholecalciferol, K1 phytonadione, K2 MK-7, sodium molybdate,cholecalciferol, chromium chloride, biotin, B12 cyanocobalamin), canolaoil, sugar, natural flavors (propylene glycol, water, potassiumsorbate), inulin, cellulose gel and carboxymethylcellulose sodium, foodstarch modified, sodium hexametaphosphate, DHA algal oil, acesulfamepotassium, carrageenan, sucralose. Contains corn and soy.

PREPARATION

Ready to drink. Shake well.

STORAGE

Store in cool, dry place. Refrigerate after opening. Do not freeze.

TO REQUEST A SAMPLE

Call 866 456 9776, opt 2 or complete form: www.samples.cambrooke.com

PHENACTIN AA PLUS

Nutrients 8.5 fl oz (250 mL) Per 100 mL Calories 186 74 Calories FromFat 57 23 Protein Equivalent, g 20 8 Free Amino Acids, g 23 9Carbohydrates, g 13 5 Sugar, g 5 2 Sugar Alcohols, g 0 0 Dietary Fiber,g 2.8 1 Fat, g 6 2.4 Saturated Fat, g 0.5 0.2 Trans Fat, g 0.0 0.0 DHA,mg 150.0 60.0 Cholesterol, mg 0.4 0 Vitamin A, IU 1100.0 440.0 VitaminC, mg 40.0 16.0 Vitamin D, IU 620.0 248.0 Vitamin E, IU 10.0 4.0 VitaminK1, mcg 20.0 8.0 Vitamin K2 (MK-7), mcg 20.0 8.0 Thiamin (B1), mg 0.50.2 Riboflavin (B2), mg 0.5 0.2 Niacin (B3), mg 6.6 2.6 Vitamin B6, mg0.5 0.2 Folic Acid, mcg 186.0 74.4 Vitamin B12, mcg 1.0 0.4 PantothenicAcid (B5), mg 2.4 1.0 Biotin, mcg 10.6 4.2 Choline, mg 209.0 83.6Calcium, mg 677.0 270.8 Chromium, mcg 17.3 6.9 Copper, mg 0.2 0.1Iodine, mcg 76.0 30.4 Iron, mg 8.0 3.2 Magnesium, mg 143.0 57.2Manganese, mg 1.0 0.4 Molybdenum, mcg 20.0 8.0 Phosphorus, mg 664.0265.6 Selenium, mcg 26.6 10.6 Zinc, mg 5.0 2.0 Potassium, mg 573.0 229.2Sodium, mg 287.0 114.8 Chloride, mg 350.0 140.0 Inositol, mg 0.0 0.0L-alanine, mg 423.0 169.2 L-arginine, mg 951.0 380.4 L-asparagine, mg0.0 0.0 L-aspartate, mg 1760.0 704.0 L-carnitine, mg 18.0 7.2 L-cystine,mg 245.4 98.2 L-glutamate, mg 0.0 0.0 L-glycine, mg 689.0 275.6L-histidine, mg 882.0 352.8 L-isoleucine, mg 1570.0 628.0 L-leucine, mg4700.0 1880.0 L-lysine, mg 1830.0 732.0 L-methionine, mg 570.0 228.0L-phenylalanine, mg 0.0 0.0 L-proline, mg 1700.0 680.0 L-serine, mg1220.0 488.0 L-taurine, mg 75.0 30.0 L-threonine, mg 1590.0 636.0L-tryptophan, mg 480.0 192.0 L-tyrosine, mg 1549.7 619.9 L-valine, mg1800.0 720.0

FIG. 6 shows a non-limiting embodiment of a product label for anutritional composition for dietary management of Methylmalonic Acidemiaand Propionic Acidemia (MMA/PA).

SKU 37003

NET WEIGHT 2 GAL (7.5 L)

SERVING SIZE 8.5 fl oz (250 mL)

SERVINGS PER PACKAGE 30

REIMBURSEMENT CODE 24359-0703-03 (for USA only)

MEDICAL FOOD PRODUCT

For the dietary management of Methylmalonic Acidemia and PropionicAcidemia (MMA/PA). Dispensed by prescription. Promactin AA Plus is aready-to-drink metabolic formula product for Propionic Acidemia andMethylmalonic Acidemia patients, over 1 year of age. Promactin containsan advanced fortification blend. Product comes in a 250 mL carton.

PRECAUTIONS For the dietary management of Methylmalonic Acidemia (MMA)and Propionic Acidemia (PA). Use as directed by physician. Must beadministered under medical supervision only.

NOT FOR PARENTERAL USE•USE AS DIRECTED BY PHYSICIAN INGREDIENTS

Water, amino acid blend (L-leucine, L-aspartic, L-lysine HCl, L-alanine,L-arginine, L-serine, L-histidine, L-tyrosine, L-phenylalanine,L-proline, L-glysine, L-cystine, L-tryptophan, L-isoleucine, taurine,L-carnitine, maltodextrin), vitamins and minerals (calcium lactate,monosodium phosphate, monopotassium phosphate, choline bitartrate,magnesium amino acid chelate, sodium ascorbate, ascorbic acid,dl-alpha-tocopheryl acetate, Fe amino acid chelate, niacinamide, zincamino acid chelate, calcium d-pantothenate, manganese sulfate,riboflavin, B6 pyridoxine HCl, thiamin HCl, copper gluconate, folicacid, vitamin A palmitate, potassium iodide, sodium selenite,cholecalciferol, K1 phytonadione, K2 MK-7, sodium molybdate,cholecalciferol, chromium chloride, biotin, B12 cyanocobalamin), canolaoil, sugar, natural flavors (propylene glycol, water, potassiumsorbate), cellulose gel and carboxymethylcellulose sodium, food starchmodified, sodium hexametaphosphate, DHA algal oil, acesulfame potassium,carrageenan, sucralose. Contains corn and soy.

PREPARATION

Ready to drink. Shake well.

STORAGE

Store in cool, dry place. Refrigerate after opening. Do not freeze.

TO REQUEST A SAMPLE

Call 866 456 9776, opt 2 or complete form: www.samples.cambrooke.com

PROMACTIN AA PLUS

Nutrients 8.5 fl oz (250 mL) Per 100 mL Calories 183 73 Calories FromFat 57 23 Protein Equivalent, g 20 8 Free Amino Acids, g 23 9Carbohydrates, g 12 5 Sugar, g 5 2 Sugar Alcohols, g 0 0 Dietary Fiber,g 1 0 Fat, g 6.0 2.4 Saturated Fat, g 0.5 0.2 Trans Fat, g 0.0 0.0 DHA,mg 150.0 60.0 Cholesterol, mg 0.4 0 Vitamin A, IU 1100.0 440.0 VitaminC, mg 40.0 16.0 Vitamin D, IU 620.0 248.0 Vitamin E, IU 10.0 4.0 VitaminK1, mcg 20.0 8.0 Vitamin K2 (MK-7), mcg 20.0 8.0 Thiamin (B1), mg 0.50.2 Riboflavin (B2), mg 0.5 0.2 Niacin (B3), mg 6.6 2.6 Vitamin B6, mg0.5 0.2 Folic Acid, mcg 186.0 74.4 Vitamin B12, mcg 1.0 0.4 PantothenicAcid (B5), mg 2.4 1.0 Biotin, mcg 10.6 4.2 Choline, mg 209.0 83.6Calcium, mg 700.0 280.0 Chromium, mcg 17.3 6.9 Copper, mg 0.2 0.1Iodine, mcg 76.0 30.4 Iron, mg 8.0 3.2 Magnesium, mg 143.0 57.2Manganese, mg 1.0 0.4 Molybdenum, mcg 20.0 8.0 Phosphorus, mg 664.0265.6 Selenium, mcg 26.6 10.6 Zinc, mg 5.0 2.0 Potassium, mg 573.0 229.2Sodium, mg 287.0 114.8 Chloride, mg 607.0 242.8 Inositol, mg 0.0 0.0L-alanine, mg 2270.0 908.0 L-arginine, mg 2178.0 871.2 L-asparagine, mg0.0 0.0 L-aspartate, mg 2900.0 1160.0 L-carnitine, mg 20.0 8.0L-cystine, mg 277.6 111.0 L-glutamate, mg 0.0 0.0 L-glycine, mg 107.042.8 L-histidine, mg 1450.0 580.0 L-isoleucine, mg 68.0 27.2 L-leucine,mg 3130.0 1252.0 L-lysine, mg 2280.0 912.0 L-methionine, mg 0.0 0.0L-phenylalanine, mg 1420.0 568.0 L-proline, mg 1020.0 408.0 L-serine, mg1480.0 592.0 L-taurine, mg 57.0 22.8 L-threonine, mg 0.0 0.0L-tryptophan, mg 613.0 245.2 L-tyrosine, mg 971.5 388.6 L-valine, mg 0.00.0

FIG. 7 shows a non-limiting embodiment of a product label for anutritional composition for dietary management of Maple Syrup UrineDisease (MSUD).

SKU 37004

NET WEIGHT 2 GAL (7.5 L)

SERVING SIZE 8.5 fl oz (250 mL)

SERVINGS PER PACKAGE 30

REIMBURSEMENT CODE 24359-0704-03 (for USA only)

MEDICAL FOOD PRODUCT

For the dietary management of Maple Syrup Urine Disease (MSUD).Dispensed by prescription. Vilactin AA Plus is a ready-to-drinkmetabolic formula product for MSUD patients, over 1 year of age.Vilactin AA Plus contains an advanced fortification blend. Comes in a250 mL carton.PRECAUTIONS For the dietary management of Maple Syrup Urine Disease(MSUD). Use as directed by physician. Must be administered under medicalsupervision only.

NOT FOR PARENTERAL USE•USE AS DIRECTED BY PHYSICIAN INGREDIENTS

Water, amino acid blend (L-glutamine, L-alanine, L-lysine HCl,L-phenylalanine, L-tyrosine, L-threonine, L-histidine, L-proline,asparagine, L-tryptophan, L-arginine, L-serine, L-glutamic acid,glycine, L-cystine, L-methionine, taurine, L-carnitine), vitamins andminerals (calcium lactate, monosodium phosphate, monopotassiumphosphate, choline bitartrate, magnesium amino acid chelate, sodiumascorbate, ascorbic acid, dl-alpha-tocopheryl acetate, iron amino acidchelate, niacinamide, zinc amino acid chelate, calcium d-pantothenate,manganese sulfate, riboflavin, B6 Pyridoxal Phosphate, thiamin HCl,copper gluconate, L-methylfolate, vitamin A palmitate, potassium iodide,sodium selenite, cholecalciferol, K1 phytonadione, K2 MK-7, sodiummolybdate, cholecalciferol, chromium chloride, biotin, B12methylcobalamin), canola oil, sugar, natural flavors (propylene glycol,water, potassium sorbate), inulin, cellulose gel andcarboxymethylcellulose sodium, food starch modified, sodiumhexametaphosphate, DHA algal oil, acesulfame potassium, carrageenan,sucralose. Contains corn and soy.

PREPARATION

Ready to drink. Shake well.

STORAGE

Store in cool, dry place. Refrigerate after opening. Do not freeze.

TO REQUEST A SAMPLE

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VILACTIN AA PLUS

Nutrients 8.5 fl oz (250 mL) Per 100 mL Calories 183 73 Calories FromFat 57 23 Protein Equivalent, g 20 8 Free Amino Acids, g 23 9Carbohydrates, g 13 5 Sugar, g 5 2 Sugar Alcohols, g 0 0 Dietary Fiber,g 3 1 Fat, g 6.0 2.4 Saturated Fat, g 0.3 0.1 Trans Fat, g 0.0 0.0 DHA,mg 150.0 60.0 Cholesterol, mg 0 0 Vitamin A, IU 1100.0 440.0 Vitamin C,mg 40.0 16.0 Vitamin D, IU 620.0 248.0 Vitamin E, IU 10.0 4.0 VitaminK1, mcg 20.0 8.0 Vitamin K2 (MK-7), mcg 20.0 8.0 Thiamin (B1), mg 0.50.2 Riboflavin (B2), mg 0.5 0.2 Niacin (B3), mg 6.6 2.6 Vitamin B6, mg0.5 0.2 Folic Acid, mcg 186.0 74.4 Vitamin B12, mcg 1.0 0.4 PantothenicAcid (B5), mg 2.4 1.0 Biotin, mcg 10.6 4.2 Choline, mg 98.3 39.3Calcium, mg 677.0 270.8 Chromium, mcg 17.4 7.0 Copper, mg 0.2 0.1Iodine, mcg 76.0 30.4 Iron, mg 8.0 3.2 Magnesium, mg 143.0 57.2Manganese, mg 1.0 0.4 Molybdenum, mcg 20.0 8.0 Phosphorus, mg 664.0265.6 Selenium, mcg 26.6 10.6 Zinc, mg 5.0 2.0 Potassium, mg 573.0 229.2Sodium, mg 287.0 114.8 Chloride, mg 350.0 140.0 Inositol, mg 0.0 0.0L-alanine, mg 2591.0 1036.4 L-arginine, mg 2085.0 834.0 L-asparagine, mg1477.0 590.8 L-aspartate, mg 0.0 0.0 L-carnitine, mg 40.0 16.0L-cystine, mg 565.0 226.0 L-glutamate, mg 0.0 0.0 L-glycine, mg 1416.0566.4 L-histidine, mg 1475.0 590.0 L-isoleucine, mg 0.0 0.0 L-leucine,mg 0.0 0.0 L-lysine, mg 1808.0 723.2 L-methionine, mg 677.0 270.8L-phenylalanine, mg 1533.0 613.2 L-proline, mg 2551.0 1020.4 L-serine,mg 1607.0 642.8 L-taurine, mg 748.0 299.2 L-threonine, mg 1734.0 693.6L-tryptophan, mg 1614.0 645.6 L-tyrosine, mg 1658.0 663.2 L-valine, mg0.0 0.0

DETAILED DESCRIPTION OF INVENTION

The disclosure relates to compositions for dietary management of inbornerrors of metabolism. Compositions for support bone health of subjectshaving inborn errors of metabolism, provide a source of completenutrition to subjects having inborn errors of metabolism, or supportbone health and provide source of complete nutrition to subjects havinginborn errors of metabolism. The term “nutritionally complete” refers toa composition having a complete nutritional profile of macro andmicronutrients (e.g., containing carbohydrates, protein, fats, vitaminsand minerals) for subjects 1 year of age and older.

Inborn Errors of Metabolism

In some aspects, the disclosure relates to compositions for dietarymanagement of inborn errors of metabolism. As used herein the term“inborn error of metabolism” refers to a disease or disordercharacterized by defective function of a metabolic enzyme. Generally, aninborn error of metabolism is inherited (e.g., a congenital disease ordisorder). Inborn errors of metabolism can be divided into severaltypes, including disorders of carbohydrate metabolism (e.g., glycogenstorage disease), disorders of amino acid metabolism, urea cycledisorders (e.g., carbamoyl phosphate synthetase I deficiency), disordersof organic acid metabolism (e.g., alcaptonuria), disorders ofmitochondrial metabolism (e.g., Leigh syndrome), disorders of fatty acidoxidation (e.g., Medium-chain acyl-coenzyme A dehydrogenase deficiency),and lysosomal storage disorders (e.g., Gaucher's disease).

In some embodiments, compositions described by the disclosure are fordietary management of disorders of amino acid metabolism, which arecharacterized by the inability of a subject to metabolize a particularamino acid. Examples of disorders of amino acid metabolism and thegene(s) associated with each disease include phenylketonuria (PKU;phenylalanine hydroxylase), Maple Syrup Urine Disease (MSUD;branched-chain alpha-keto acid dehydrogenase complex), Homocystinuria(HCU; cystathionine beta synthase), Isovaleric acidaemia (IVA;isovaleric acid-CoA dehydrogenase), and Methylmalonicacidaemia/Propionic acidaemia (MMA/PA; methylmalonyl-CoAmutase/propionyl-CoA carboxylase).

Nutritional Formulas for Dietary Management of Inborn Errors ofMetabolism

In some aspects, the disclosure provides a nutritional composition fordietary management of an inborn error of metabolism comprising: aprotein source, a fat source, a carbohydrate source, and a bone healthcomposition, wherein the protein source comprises at least six freeamino acids. In some embodiments, the nutritional composition isnutritionally complete.

The protein source is a mixture of free amino acids. As used herein, theterm “free amino acid” refers to a single amino acid that does notrequire digestion or metabolism. Generally, a free amino acid is to theL-isomer of the amino acid (e.g., L-alanine) as opposed to the D-isomerof the amino acid (e.g., D-alanine). However, in some embodiments, afree amino acid is the D-isomer of the amino acid.

In some embodiments, a protein source comprises a mixture of free aminoacids (e.g., a blend of amino acids). Such a mixture of amino acidcomprises essential amino acids and non-essential amino acids. Theessential amino acids are histidine, isoleucine, leucine, lysine,methionine, phenylalanine, threonine, tryptophan, and valine. The aminoacids present in a particular amino acid mixture of a protein sourcewill be determined by the inborn error of metabolism to be managed byadministration of the nutritional composition. For example, acomposition for the management of phenylketonuria will have, at most, aminimal amount of phenylalanine. In some embodiments, a protein source(e.g., a blend of amino acids) comprises at least six free amino acids.In some embodiments, the at least six free amino acids are selected fromthe group consisting of: histidine, isoleucine, leucine, lysine,methionine, phenylalanine, threonine, tryptophan, and valine. Examplesof protein source blends are shown in Table 3, Table 4, Table 6, Table8, Table 9, and Table 10.

Amino acid content affects the pH of nutritional compositions. In someembodiments, the pH of a nutritional composition described by thedisclosure ranges from about pH 3.0 to about pH 7.0. In someembodiments, the pH of a nutritional composition described by thedisclosure ranges from about pH 4.0 to about pH 6.0. In someembodiments, the pH of a nutritional composition described by thedisclosure ranges from about pH 5.0 to about pH 6.0. In someembodiments, the pH of a nutritional composition described by thedisclosure is about pH 4.0, pH 4.1, pH 4.2, pH 4.3, pH 4.4, pH 4.5, pH4.6, pH 4.7, pH 4.8, pH 4.9, pH 5.0, pH 5.1, pH 5.2, pH 5.3, pH 5.4, pH5.5, pH 5.6, pH 5.7, pH 5.8, pH 5.9, or pH 6.0. In some embodiments, thepH of a nutritional composition is less than pH 5.0.

The nutritional compositions as described herein comprise a fat source,which can be a single type of fat, or a combination of more than onetype of fat. A fat source may comprise saturated fats, unsaturated fatsor a combination of saturated fats and unsaturated fats. Fat cancomprise long chain fatty acids, short chain fatty acids or acombination of long chain fatty acids and short chain fatty acids. Insome embodiments, fat comprises triglycerides, such as short-chaintriglycerides, long-chain triglycerides, medium-chain triglycerides or acombination of two or three of the foregoing (e.g., short-chaintriglycerides, long-chain triglycerides and medium-chain triglycerides;short-chain triglycerides and long-chain triglycerides; short-chaintriglycerides and medium-chain triglycerides; medium-chain triglyceridesand long-chain triglycerides). Examples of fat sources include but arenot limited to: butter, animal fat (for example beef or chicken fat),vegetable oil (for example avocado, corn, and soybean), olive oil,canola oil, coconut oil, cocoa butter, fish oil, nuts (for examplemacadamia and peanut) and nut oils.

In some embodiments, the fat source is between about 1.8% and about 2.8%of the total weight of the composition. In some embodiments, the fatsource is about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%,about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, or about2.8% of the total weight of the composition. In some embodiments, thefat source is at a concentration of between about 19 g/L and about 29g/L.

Emulsifiers can be used to improve stability and texture of nutritionalcompositions described herein. In some aspects, the nutritionalcompositions comprise an emulsifier or emulsifying agent (e.g., asurfactant), such as sodium stearoyl lactylate (SSL), lecithin,starches, gums and biopolymeric emulsifiers. In some embodiments, theemulsifier is a modified starch, such as octenyl succinate starch (e.g.,OSA starch) or other modified starch, that interferes with interactionof fat and protein source in the formula, such as by binding of theoctenyl moiety of the starch to fat globules.

Nutritional compositions comprise a carbohydrate source, such as starch,gum and/or fiber. In some embodiments, carbohydrate acts as a foodstabilizer. A carbohydrate source can be a single type of carbohydrate,or a combination of several types of carbohydrate. In some embodiments,carbohydrate is less than about 2.1% of the total weight of thecomposition. In some embodiments, carbohydrate is a gum. In someembodiments, carbohydrate comprises carboxymethyl cellulose, carrageenanor carboxymethyl cellulose and carrageenan.

In some embodiments, the composition contains supplemental dietaryfiber. Dietary fiber can be a single type of fiber or a combination ofmore than one type of fiber. In some embodiments, the dietary fibers aresoluble fibers, non-soluble fibers, or dietary fibers and non-solublefibers. In some embodiments, the fiber comprises very low densitylipoprotein (vldl)- and low density lipoprotein (ldl)-reducing solublefibers. In some embodiments, the fiber is one or more selected from thegroup consisting of inulin, pectin, cellulose gum (carboxymethylcellulose) and carrageenan.

In some embodiments, nutritional compositions further comprise at leastone (one or more) sweetener, such as acesulfame potassium, sucralose,aspartame, lo han guo, stevia, erythritol, xylitol, maltitol, sorbitol,other nutritive or non-nutritive sources. In some embodiments, thecomposition does not contain artificial or nutritive sweeteners.

The nutritional compositions described herein comprise at least onevitamin and at least one mineral. In some embodiments, the at least onevitamin is selected from the group consisting of Vitamin A, Vitamin D,Vitamin E, Biotin, folic acid, niacin, pantothenic acid, Vitamin B1,Vitamin B12, Vitamin B2, Vitamin B6, Vitamin C, and Vitamin K. Examplesof vitamin sources include: palmitates, beta-carotene, ergocalciferol,cholecalciferol, dl-alpha tocopheryl acetate, d-alpha tocopherylacetate, dl-alpha tocotrienols, calcium panthothenate, pantothenol,pantothenic acid, cyanocobalamin, methylcobalamin, sodium ascorbate,calcium ascorbate, ascorbic acid, pyridoxine hydrochloride, pyridoxal5′phosphate, riboflavin, thiamin, folic acid, phylloquinone,phytomenadione, phytonadione, menaquinones (e.g., MK-4 and MK-7) andbiotin. Any combination of vitamins can be included in the nutritionalcompositions. In some embodiments, a nutritional composition comprisesat least one vitamin in an amount listed in Table 2 or Table 7. In someembodiments, a nutritional composition comprises all of the vitamins inTable 2 or Table 7, such as the vitamins listed in the quantities listedin Table 2 or Table 7.

In some embodiments, the nutritional composition comprises at least onemineral selected from the group consisting of: calcium, chromium,copper, iodine, iron, magnesium, manganese, molybdenum, phosphorus,potassium, selenium, sodium, and zinc. Examples of mineral sourcesinclude calcium lactate, calcium gluconate, calcium pantothenate,calcium lactate gluconate, calcium phosphate, calcium carbonate, calciumcitrate, calcium phosphate, magnesium phosphate, potassium phosphate,choline chloride, phosphatidylcholine, choline bitartrate, lecithin,magnesium chloride, magnesium oxide, magnesium gluconate, magnesiumphosphate, magnesium malate, magnesium citrate, magnesium fumarate,inositol hexanicotinate, nicotinamide, niacinamine, zinc carbonate, zinccitrate, zinc sulfate, zinc gluconate, zinc bisglycinate, zinc fumarate,manganese chloride, manganese gluconate, manganese sulfate, manganesepicolinate, monosodium sulfate, monopotassium phosphate, iron sulfate,iron citrate, iron gluconate, ferrous fumarate, cupric oxide, coppergluconate, copper sulfate, copper carbonate, chromium picolinate,chromium chloride, chromium polynicotinate, chromium chloride, sodiumchloride, potassium chloride, magnesium chloride, manganese chloride,choline chloride, potassium chloride, potassium citrate, potassiumiodide, potassium sodium tartrate, potassium bisulfite, potassiumiodide, sodium selenite, selenomethionine, sodium selenite, potassiummolybdate, sodium molybdate, sodium chloride, sodium citrate, or aminoacid chelates (e.g., zinc chelate, magnesium chelate) of any of theforegoing. Any combination of minerals can be included in thenutritional compositions. In some embodiments, a nutritional compositioncomprises at least one mineral in an amount listed in Table 2 or Table7. In some embodiments, a nutritional composition comprises all of theminerals listed in Table 2 or Table 7, such as the minerals in thequantities listed in Table 2 or Table 7.

The addition of certain minerals, such as zinc, copper and/or iron, tofood products is known to contribute to fat rancidity in food products.Chelation of sensitive minerals may therefore reduce fat rancidity bypreventing minerals associated with fat rancidity from interacting withfats that are present in a composition. In some embodiments, thenutritional compositions comprise a chelating agent, such as phosphatesor phosphonates, EDTA and sodium hexametaphosphate (SHMP). In someembodiments, the chelating agent is sodium hexametaphosphate (SHMP).Other methods of reducing fat rancidity, such as the addition ofantioxidants, are also known in the art. In some embodiments,nutritional compositions described herein comprise at least oneantioxidant, such as ascorbate, ascorbic acid (Vitamin C), cysteine andtocopherols.

Several embodiments of a nutritionally complete nutritional compositionfor dietary management of an inborn error of metabolism are shown inTable 5. Table 5 provides ranges of each component of a nutritionalcomposition. In some embodiments, the amino acid blend of thecomposition is selected from the amino acid blends listed in Table 4 orTable 10. The amino acid blend of the composition is determined by theinborn error of metabolism to be managed by the composition. Forexample, if the condition to be managed is MSUD, Blend #2 from Table 4or Blend #2 from Table 10 can be used. In some embodiments, the vitaminand mineral blend referred to Table 5 comprises the vitamin and mineralblend represented in Table 2 or Table 7.

Compositions Supporting Bone Health

In some aspects, the disclosure relates to compositions that supportbone health in subjects having inborn errors of metabolism. Subjectshaving certain types of inborn errors of metabolism have increased riskof bone abnormalities (e.g., reduced bone mineral density). Accordinglyin some embodiments, the disclosure provides compositions that supportthe bone health of subjects having inborn errors of metabolism. Bonehealth compositions can be solid (e.g., a powder) or liquid.

Bone health compositions described herein comprise vitamins andminerals. In some embodiments, bone health compositions comprise VitaminD, calcium, phosphorus, zinc, magnesium, and Vitamin K. For example, theamount of each component in about 1.5 g (without inulin) to about 4.0 g(with inulin) of bone health composition described by the disclosure isshown in Table 1. The amount of bone health composition included in aserving of nutritional composition ranges from about 0.5 g to about 5.0g. In some embodiments, the amount of bone health composition includedin a serving of nutritional composition ranges from about 1.0 g to about4.0 g. In some embodiments, the amount of bone health compositionincluded in a serving of nutritional composition ranges from about 1.5 gto about 3.5 g. In some embodiments, the amount of bone healthcomposition included in a serving of nutritional composition ranges fromabout 2.0 g to about 3.0 g. In some embodiments, the amount of bonehealth composition included in a serving of nutritional composition isabout 1.5 g, about 1.6 g, about 1.7 g, about 1.8 g, about 1.9 g, about2.0 g, about 2.1 g, about 2.2 g, about 2.3 g, about 2.4 g, about 2.5 g,about 2.6 g, about 2.7 g, about 2.8 g, about 2.9 g, about 3.0 g, about3.1 g, about 3.2 g, about 3.3 g, about 3.4 g, about 3.5 g, about 3.6 g,about 3.7 g, about 3.8 g, about 3.9 g, or about 4.0 g.

In some embodiments, bone health compositions are added to supplementnutritional formulas and compositions for dietary management of inbornerrors of metabolism. For example, a bone health composition may becombined with a protein source. In some embodiments, the protein sourcecomprises one or more amino acids selected from the group consisting of:histidine, isoleucine, leucine, lysine, methionine, phenylalanine,threonine, tryptophan, and valine. In some embodiments, the proteinsource comprises at least six amino acids selected from the groupconsisting of: histidine, isoleucine, leucine, lysine, methionine,phenylalanine, threonine, tryptophan, and valine.

TABLE 1 Ranges of Components in Bone Health Compositions Minimum MaximumVitamin/Mineral Amount Amount vitamin D3 (IU) 500 770 calcium (mg) 550840 phosphorus (mg) 475 720 zinc (mg) 4 6 magnesium (mg) 125 195 vitaminK1 (mcg) 10 25 vitamin K2 (mcg) 10 25 inulin (g) 0 2.5

TABLE 2 Examples of Ranges of Vitamins and Minerals in NutritionalCompositions Minimum Maximum Vitamin/Mineral Amount Amount Vitamin A(IU) 950 1450 Vitamin D3 (IU) 500 770 Vitamin E (IU) 7 12 Biotin (μg) 813 Folic Acid (mg) 0.14 0.23 Niacin (mg) 5.25 7.95 Pantothenic Acid (mg)1.9 2.9 Vitamin B1 (mg) 0.43 0.65 Vitamin B12 (μg) 0.75 1.2 Vitamin B2(mg) 0.43 0.65 Vitamin B6 (mg) 0.43 0.65 Vitamin C (mg) 35 55 Vitamin K1(μg) 10 25 Vitamin K2 (μg) 10 25 Calcium (mg) 550 840 Chromium (μg) 13.520.9 Copper (mg) 0.15 0.25 Iodine (μg) 60 91.5 Iron (mg) 6 9.75Magnesium (mg) 125 195 Manganese (mg) 0.75 1.25 Molybdenum (μg) 15 25Phosphorus (mg) 475 720 Potassium (mg) 375 570 Selenium (μg) 21 32Sodium (mg) 100 200 Zinc (mg) 4 6 sodium ascorbate 0.06 0.09 ascorbicacid 0.03 0.05

TABLE 3 Examples of Free Amino Acid Ranges in Nutritional CompositionsAA Blend/Serving Minimum Maximum (8.5 fl oz.) mg/serving mg/servingGlycine (mg) 85 2510 L-Alanine (mg) 360 5000 L-Arginine (mg) 435 2500L-Asparagine (mg) 0 2070 L-Aspartic Acid (mg) 0 2900 L-Carnitine (mg) 151140 L-Cystine (mg) 190 865 L-Glutamic Acid (mg) 0 400 L-Glutamine (mg)195 2870 L-Histidine (mg) 510 1450 L-Isoleucine (mg) 0 1570 L-Leucine(mg) 0 4710 L-Lysine (mg) 775 2300 L-Methionine (mg) 0 600L-Phenylalanine (mg) 0 1500 L-Proline (mg) 500 2160 L-Serine (mg) 3801485 L-Threonine (mg) 0 1600 L-Tryptophan (mg) 195 615 L-Tyrosine (mg)375 2260 L-Valine (mg) 0 1800 Taurine 35 80

TABLE 4 Examples of Amino Acid Blends Blend 1 Blend 2 Blend 3 Blend 4Blend 5 Amino Acid/ (PKU) (MSUD) (HCU) (MMA/PA) (IVA) 8 fl oz.servingMIN MAX MIN MAX MIN MAX MIN MAX MIN MAX Glycine (mg) 551.2 827 216 3241200 1800 781.6 1172.4 1745.6 2618 L-Alanine (mg) 338.4 508 864 1296 8561284 1816 2724 3479.2 5219 L-Arginine (mg) 760.8 1141 408 612 1240 18601742.4 2613.6 1522.4 2284 L-Asparagine (mg) 0 0 464 696 0 0 0 0 0 0L-Aspartic Acid (mg) 1408.8 2113 0 0 1549.6 2324 2320 3480 894.4 1342L-Carnitine (mg) 14.4 21.6 16 24 16.8 25.2 16 24 910.4 1366 L-Cystine(mg) 621.6 932 176 264 648 972 689.6 1034.4 178.4 268 L-Glutamic Acid(mg) 0 0 280 420 0 0 0 0 0 0 L-Glutamine (mg) 184.8 277 2296 3444 1025.61538 964 1446 1496 2244 L-Histidine (mg) 705.6 1058 568 852 744 11161162.4 1743.6 480 720 L-Isoleucine (mg) 1256 1884 0 0 1146.4 1720 54.481.6 509.6 764 L-Leucine (mg) 3765.6 5648 0 0 1965.6 2948 2504 3756 0 0L-Lysine (mg) 1468 2202 728 1092 1296 1944 1826.4 2739.6 1159.2 1739L-Methionine (mg) 461.6 692 240 360 0 0 0 0 344.8 517 L-Phenylalanine(mg) 0 0 704 1056 864 1296 1142.4 1713.6 988.8 1483 L-Proline (mg)1364.8 2047 472 708 1408 2112 822.4 1233.6 1725.6 2588 L-Serine (mg)980.8 1471 360 540 1005.6 1508 1186.4 1779.6 933.6 1400 L-Threonine (mg)1276.8 1915 576 864 914.4 1372 0 0 840 1260 L-Tryptophan (mg) 385.6 578424 636 386.4 580 490.4 735.6 183.2 275 L-Tyrosine (mg) 1804.8 2707 7041056 1128 1692 1142.4 1713.6 993.6 1490 L-Valine (mg) 1440.8 2161 0 01250.4 1876 0 0 573.6 860

TABLE 5 Example of a Nutritional Composition Minimum Maximum Minimum %Maximum % Ingredient g/L g/L Total Weight Total Weight Water 890 75072.47%  87.5% stabilizer blend 4 6.2 0.39% 0.610%  sequestrant 1 1.6 0.1% 0.12% choline 0 1   0%  0.1% carbohydrate blend 9 15 0.87% 1.48%fiber blend 5 10 0.48% 0.98% Emulsifier 1.9 2.9 0.18% 0.29% fat blend 1929 1.84% 2.85% amino acid blend 80 140 7.73% 13.76%  vitamin and 25 402.42% 3.93% mineral blend Sweetener 0 1.5   0% 0.15% Flavor 0 20   0%1.97%

TABLE 6 Examples of Amino Acid Blends in Nutritional Compositions AABlend 1 Blend 2 Blend 3 Blend 4 Blend 5 AA Blend/Serving Blend/Serving(PKU) (MSUD) (HCU) (MMA/PA) (IVA) Glycine (mg) 689 270 1500 977 2182 100L-Alanine (mg) 423 1080 1070 2270 4349 1000 L-Arginine (mg) 951 510 15502178 1903 2000 L-Asparagine (mg) 0 580 0 0 0 1800 L-Aspartic Acid (mg)1761 0 1937 2900 1118 1200 L-Carnitine (mg) 18 20 21 20 1138 L-Cystine(mg) 777 220 810 862 223 600 L-Glutamic Acid 0 350 0 0 0 400 (mg)L-Glutamine (mg) 231 2870 1282 1205 1870 1600 L-Histidine (mg) 882 710930 1453 600 800 L-Isoleucine (mg) 1570 0 1433 68 637 0 L-Leucine (mg)4707 0 2457 3130 0 1500 L-Lysine (mg) 1835 910 1620 2283 1449 2300L-Methionine (mg) 577 300 0 0 431 600 L-Phenylalanine 0 880 1080 14281236 1500 (mg) L-Proline (mg) 1706 590 1760 1028 2157 600 L-Serine (mg)1226 450 1257 1483 1167 1000 L-Threonine (mg) 1596 720 1143 0 1050 500L-Tryptophan (mg) 482 530 483 613 229 480 L-Tyrosine (mg) 2256 880 14101428 1242 440 L-Valine (mg) 1801 0 1563 0 717 500 Taurine 75 60 50 57 4380

TABLE 7 Examples of Ranges of Vitamins and Minerals in NutritionalCompositions Minimum Maximum Vitamin/Mineral Amount Amount Vitamin A(IU) 950 1450 Vitamin D3 (IU) 500 770 Vitamin E (IU) 7 12 Biotin (μg) 813 Folic Acid (mg) 0.14 0.23 Niacin (mg) 5.25 7.95 Pantothenic Acid (mg)1.9 2.9 Vitamin B1 (mg) 0.43 0.65 Vitamin B12 (μg) 0.75 1.2 Vitamin B2(mg) 0.43 0.65 Vitamin B6 (mg) 0.43 0.65 Vitamin C (mg) 35 55 Vitamin K1(μg) 10 25 Vitamin K2 (μg) 10 25 Calcium (mg) 550 840 Chromium (μg) 13.520.9 Copper (mg) 0.15 0.25 Iodine (μg) 60 91.5 Iron (mg) 6 9.75Magnesium (mg) 125 195 Manganese (mg) 0.75 1.25 Molybdenum (μg) 15 25Phosphorus (mg) 475 720 Potassium (mg) 375 600 Selenium (μg) 21 32Sodium (mg) 100 300 Chloride (mg) 10 700 Zinc (mg) 4 6 sodium ascorbate0.06 0.09 ascorbic acid 0.03 0.05

TABLE 8 Examples of Free Amino Acid Ranges in Nutritional CompositionsMin Max AA/Serving (8.5 fl oz.) mg/serving mg/serving Glycine (mg) 85.62616 L-Alanine (mg) 338.4 5208 L-Arginine (mg) 760.8 2613.6 L-Asparagine(mg) 0 1772.4 L-Aspartic Acid (mg) 0 3480 L-Carnitine (mg) 14.4 1236L-Cystine (mg) 129.52 678 L-Glutamic Acid (mg) 0 0 L-Histidine (mg) 4801770 L-Isoleucine (mg) 0 1884 L-Leucine (mg) 0 5640 L-Lysine (mg) 11522736 L-Methionine (mg) 0 812.4 L-Phenylalanine (mg) 0 1839.6 L-Proline(mg) 816 3061.2 L-Serine (mg) 928 1928.4 L-Threonine (mg) 0 2080.8L-Tryptophan (mg) 183.2 1936.8 L-Tyrosine (mg) 629.12 1989.6 L-Valine(mg) 0 2160 Taurine 34.4 897.6

TABLE 9 Examples of Amino Acid Blends in Nutritional Compositions Blend4 AA Blend/Serving Blend 1 Blend 2 Blend 3 (MMA/ Blend 5 (8.5 fl oz.)(PKU) (MSUD) (HCU) PA) (IVA) Glycine (mg) 689 1416 1500 107 2180L-Alanine (mg) 423 2591 1070 2270 4340 L-Arginine (mg) 951 2085 15502178 1900 L-Asparagine (mg) 0 1477 0 0 0 L-Aspartic Acid (mg) 1761 01930 2900 1110 L-Carnitine (mg) 18 40 21 20 1030 L-Cystine (mg) 245.4565 393.2 277.6 161.9 L-Glutamic Acid (mg) 0 0 0 0 0 L-Histidine (mg)882 1475 930 1450 600 L-Isoleucine (mg) 1570 0 1430 68 630 L-Leucine(mg) 4700 0 2450 3130 0 L-Lysine (mg) 1830 1808 1620 2280 1440L-Methionine (mg) 570 677 0 0 431 L-Phenylalanine (mg) 0 1533 1080 14201230 L-Proline (mg) 1700 2551 1760 1020 2150 L-Serine (mg) 1220 16071250 1480 1160 L-Threonine (mg) 1590 1734 1140 0 1050 L-Tryptophan (mg)480 1614 480 613 229 L-Tyrosine (mg) 1549.7 1658 786.4 971.5 994.6L-Valine (mg) 1800 0 1560 0 717 Taurine 75 748 50 57 43

TABLE 10 Examples of Amino Acid Blends AA Blend 1 Blend 2 Blend 3 Blend4 Blend 5 Blend/Serving (PKU) (MSUD) (HCU) (MMA/PA) (IVA) (8.5 fl oz.)MIN MAX MIN MAX MIN MAX MIN MAX MIN MAX Glycine (mg) 551.2 826.8 11331699 1200 1800 85.6 128.4 1744 2616 L-Alanine (mg) 338.4 507.6 2073 3109856 1284 1816 2724 3472 5208 L-Arginine 760.8 1141.2 1668 2502 1240 18601742.4 2613.6 1520 2280 (mg) L-Asparagine 0 0 1182 1772 0 0 0 0 0 0 (mg)L-Aspartic Acid 1408.8 2113.2 0 0 1544 2316 2320 3480 888 1332 (mg)L-Carnitine 14.4 21.6 32 48 16.8 25.2 16 24 824 1236 (mg) L-Cystine (mg)196.3 294.5 452 678 314.6 471.8 222.1 333.1 129.5 194.3 L-Glutamic 0 0 00 0 0 0 0 0 0 Acid (mg) L-Histidine 705.6 1058.4 1180 1770 744 1116 11601740 480 720 (mg) L-Isoleucine 1256 1884 0 0 1144 1716 54.4 81.6 504 756(mg) L-Leucine (mg) 3760 5640 0 0 1960 2940 2504 3756 0 0 L-Lysine (mg)1464 2196 1446 2170 1296 1944 1824 2736 1152 1728 L-Methionine 456 684541.6 812.4 0 0 0 0 344.8 517.2 (mg) L-Phenylalanine 0 0 1226 1840 8641296 1136 1704 984 1476 (mg) L-Proline (mg) 1360 2040 2041 3061 14082112 816 1224 1720 2580 L-Serine (mg) 976 1464 1286 1928 1000 1500 11841776 928 1392 L-Threonine 1272 1908 1387 2081 912 1368 0 0 840 1260 (mg)L-Tryptophan 384 576 1291 1937 384 576 490.4 735.6 183.2 274.8 (mg)L-Tyrosine 1239.8 1859.6 1326 1990 629.12 943.68 777.2 1165.8 795.71193.5 (mg) L-Valine (mg) 1440 2160 0 0 1248 1872 0 0 573.6 860.4Taurine 60 90 598.4 897.6 40 60 45.6 68.4 34.4 51.6

TABLE 11 Nutrients HCU IVA MMA-PA MSUD PKU HOMACTIN ISOVACTIN PROMACTINVILACTIN PHENACTIN AA AA AA AA AA 8.5 FL OZ PER 8.5 FL OZ PER 8.5 FL OZPER 8.5 OZ PER 8.5 FL OZ PER Nutrients (250 ML) 100 ML (250 ML) 100 ML(250 ML) 100 ML (250 ML) 100 ML (250 ML) 100 ML Calories From Fat 57 2358 23 58 23 57 23 Protein Equivalent, g 20 8 20 8 20 8 20 8 Free AminoAcids, g 23 9 24 9 23 9 24 10 24 9 Carbohydrates, g 11 4 11 4 11 4 11 411 4 Sugar, g 3 1 3.2 1 3.2 1 3.2 1 3 1 Sugar Alcohols, g 0 0 0 0 0 0 00 Dietary Fiber, g 2.8 1 2.8 1 2.8 1 2.8 1 2.8 1 Fat, g 6.4 2.6 6.3 2.56.5 2.6 6.5 2.6 6 2.4 Saturated Fat, g 0.5 0.2 0.5 0.2 0.7 0.3 0.7 0.30.5 0.2 Trans Fat, g 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0Cholesterol, mg 0.4 0 0.4 0 0.4 0 0.3 0 0.4 0 Vitamin A, IU 1080.0 432.01080.0 432.0 1080.0 432.0 1080.0 432.0 1080.0 432.0 Vitamin C, mg 40.016.0 40.0 16.0 40.0 16.0 40.0 16.0 40.0 16.0 Vitamin D, IU 620.0 248.0620.0 248.0 620.0 248.0 620.0 248.0 620.0 248.0 Vitamin E, IU 10.0 4.010.0 4.0 10.0 4.0 10.0 4.0 10.0 4.0 Vitamin K1, mcg 20.0 8.0 20.0 8.020.0 8.0 20.0 8.0 20.0 8.0 Vitamin K2 (MK-7), mcg 20.0 8.0 20.0 8.0 20.08.0 20.0 8.0 20.0 8.0 Thiamin (B1), mg 0.5 0.2 0.5 0.2 0.5 0.2 0.5 0.20.5 0.2 Riboflavin (B2), mg 0.5 0.2 0.5 0.2 0.5 0.2 0.5 0.2 0.5 0.2Niacin (B3), mg 6.6 2.6 6.6 2.6 6.6 2.6 6.6 2.6 6.6 2.6 Vitamin B6, mg0.5 0.2 0.5 0.2 0.5 0.2 0.5 0.2 0.5 0.2 Folic acid, mcg 186.0 74.4 186.074.4 186.0 74.4 186.0 74.4 Vitamin B12, mcg 1.0 0.4 1.0 0.4 1.0 0.4 1.00.4 1.0 0.4 Pantothenic Acid (B5), mg 2.4 1.0 2.4 1.0 2.4 1.0 2.4 1.02.4 1.0 Biotin, mcg 10.6 4.2 10.6 4.2 10.6 4.2 10.6 4.2 10.6 4.2Choline, mg 209.0 83.6 209.0 83.6 209.0 83.6 209.0 83.6 209.0 83.6Calcium, mg 700.0 280.0 700.0 280.0 700.0 280.0 700.0 280.0 700.0 280.0Chromium, mcg 17.3 6.9 17.3 6.9 17.3 6.9 17.4 6.9 17.3 6.9 Copper, mg0.2 0.1 0.2 0.1 0.2 0.1 0.2 0.1 0.2 0.1 Iodine, mcg 76.0 30.4 76.0 30.476.0 30.4 76.0 30.4 76.0 30.4 Iron, mg 8.0 3.2 8.0 3.2 8.0 3.2 8.0 3.28.0 3.2 Magnesium, mg 160.0 64.0 160.0 64.0 160.0 64.0 160.0 64.0 160.064.0 Manganese, mg 1.0 0.4 1.0 0.4 1.0 0.4 1.0 0.4 1.0 0.4 Molybdenum,mcg 20.0 8.0 20.0 8.0 20.0 8.0 20.0 8.0 20.0 8.0 Phosphorus, mg 695.0278.0 695.0 278.0 695.0 278.0 695.0 278.0 695.0 278.0 Selenium, mcg 27.010.8 27.0 10.8 27.0 10.8 26.6 10.6 27.0 10.8 Zinc, mg 5.0 2.0 5.0 2.05.0 2.0 5.0 2.0 5.0 2.0 Potassium, mg 500.0 200.0 500.0 200.0 500.0200.0 500.0 200.0 500.0 200.0 Sodium, mg 233.0 93.2 233.0 93.2 233.093.2 233.0 93.2 233.0 93.2 Chloride, mg 20.0 8.0 20.0 8.0 20.0 8.0 432.0172.8 20.0 8.0 Inositol, mg 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0L-alanine, mg 1070.0 428.0 4340.0 1736.0 2270.0 908.0 2160.0 864.0 423.0169.2 L-arginine, mg 1550.0 620.0 1900.0 760.0 2178.0 871.2 1020.0 408.0951.0 380.4 L-asparagine, mg 0.0 0.0 1160.0 464.0 L-aspartate, mg 1930.0772.0 1110.0 440.0 2900.0 1160.0 0.0 0.0 1760.0 704.0 L-cystine, mg810.0 324.0 220.0 88.0 860.0 344.0 440.0 176.0 777.0 310.8 L-glutamate,mg 700.0 280.0 L-glycine, mg 1500.0 600.0 2180.0 872.0 107.0 42.8 540.0216.0 689.0 275.6 L-histidine, mg 930.0 372.0 600.0 240.0 1450.0 580.01420.0 568.0 882.0 352.8 L-isoleucine, mg 1430.0 572.0 630.0 252.0 68.027.2 0.0 0.0 1570.0 628.0 L-leucine, mg 2450.0 980.0 0.0 0.0 3130.01252.0 0.0 0.0 4700.0 1880.0 L-lysine, mg 1620.0 648.0 1440.0 576.02280.0 912.0 1820.0 728.0 1830.0 732.0 L-methionine, mg 0.0 0.0 431.0172.4 0.0 0.0 600.0 240.0 570.0 228.0 L-phenylalanine, mg 1080.0 432.01230.0 492.0 1420.0 568.0 1760.0 704.0 0.0 0.0 L-proline, mg 1760.0704.0 2150.0 860.0 1020.0 408.0 1180.0 472.0 1700.0 680.0 L-serine, mg1250.0 500.0 1160.0 464.0 1480.0 592.0 900.0 360.0 1220.0 488.0L-threonine, mg 1140.0 456.0 1050.0 420.0 0.0 0.0 1440.0 576.0 1590.0636.0 L-tryptophan, mg 480.0 192.0 229.0 91.6 613.0 245.2 1060.0 424.0480.0 192.0 L-tyrosine, mg 1410.0 564.0 1240.0 496.0 1420.0 568.0 1760.0704.0 2250.0 900.0 L-valine, mg 1560.0 624.0 717.0 286.8 0.0 0.0 0.0 0.01800.0 720.0

1. A composition comprising: Vitamin D, calcium, phosphorus, zinc,magnesium, and Vitamin K, wherein the Vitamin D is between about 500 IUand about 770 IU of the total weight of the composition, calcium isbetween about 36% and about 56% of the total weight of the composition,phosphorus is between about 31% and about 48% of the total weight of thecomposition, zinc is between about 0.25% and about 0.40% of the totalweight of the composition, magnesium is between about 8% and about 13%of the total weight of the composition, and Vitamin K is between about1.2% and about 3.5% of the total weight of the composition.
 2. Acomposition comprising Vitamin D, calcium, phosphorus, zinc, magnesium,and Vitamin K, wherein in about 1.5 g to about 4.0 g of composition,Vitamin D is between about 500 IU and 770 IU, calcium is between about500 mg and about 840 mg, phosphorus is between about 475 mg and about720 mg, zinc is between about 4 mg and about 6 mg, magnesium is betweenabout 125 mg and about 195 mg, and Vitamin K is between about 20 μg andabout 50 μg. 3-4. (canceled)
 5. The composition of claim 1, furthercomprising inulin.
 6. (canceled)
 7. The composition of claim 5, whereinfrom about 0 g to about 2.5 g inulin is present in 3.5 g of thecomposition. 8-9. (canceled)
 10. A composition comprising a compositionof claim 1 and a protein source, wherein Vitamin D is between about 500IU per 20 g Protein Equivalent (PE) and 770 IU per 20 g PE, calcium isbetween about 500 mg per 20 g PE and about 840 mg per 20 g PE,phosphorus is between about 475 mg per 20 g PE and about 720 mg per 20 gPE, zinc is between about 4 mg per 20 g PE and about 6 mg per 20 g PE,magnesium is between about 125 mg per 20 g PE and about 195 mg per 20 gPE, and the Vitamin K is between about 20 μg per 20 g PE and about 50 μgper 20 g PE.
 11. The composition of claim 10, wherein the protein sourcecomprises at least six amino acids selected from the group consistingof: histidine, isoleucine, leucine, lysine, methionine, phenylalanine,threonine, tryptophan, and valine.
 12. A nutritional composition fordietary management of an inborn error of metabolism comprising: aprotein source, a fat source, a carbohydrate source, and the compositionof claim 1, and, wherein the protein source comprises at least six freeamino acids.
 13. The nutritional composition of claim 12, wherein the pHof the composition is from about pH 5.0 to about pH 6.0. 14-15.(canceled)
 16. The nutritional composition of claim 12, wherein glycineranges from about 85 mg/20 g PE to about 2510 mg/20 g PE, alanine rangesfrom about 360 mg/20 g PE to about 5000 mg/20 g PE, arginine ranges fromabout 435 mg/20 g PE to about 2500 mg/20 g PE, asparagine ranges fromabout 0 mg/20 g PE to about 2070 mg/20 g PE, aspartic acid ranges fromabout 0 mg/20 g PE to about 2900 mg/20 g PE, cystine ranges from about190 mg/20 g PE to about 865 mg/20 g PE, glutamic acid ranges from about0 mg/20 g PE to about 400 mg/20 g PE, glutamine ranges from about 195mg/20 g PE to about 2870 mg/20 g PE, histidine ranges from about 510mg/20 g PE to about 1450 mg/20 g PE, isoleucine ranges from about 0mg/20 g PE to about 1570 mg/20 g PE, leucine ranges from about 0 mg/20 gPE to about 4710 mg/20 g PE, lysine ranges from about 775 mg/20 g PE toabout 2300 mg/20 g PE, methionine ranges from about 0 mg/20 g PE toabout 600 mg/20 g PE, phenylalanine ranges from about 0 mg/20 g PE toabout 1500 mg/20 g PE, proline ranges from about 500 mg/20 g PE to about2160 mg/20 g PE, serine ranges from about 380 mg/20 g PE to about 1485mg/20 g PE, threonine ranges from about 0 mg/20 g PE to about 1600 mg/20g PE, tryptophan ranges from about 195 mg/20 g PE to about 615 mg/20 gPE, tyrosine ranges from about 375 mg/20 g PE to about 2260 mg/20 g PE,and valine ranges from about 0 mg/20 g PE to about 1800 mg/20 g PE. 17.The nutritional composition of claim 12, further comprising at least onecomponent selected from the group consisting of carnitine, taurine, andDocosahexaenoic acid (DHA).
 18. The nutritional composition of claim 12,further comprising at least one vitamin selected from the groupconsisting of: Vitamin A, Vitamin E, biotin, folic acid, niacin,pantothenic acid, Vitamin B1, Vitamin B12, Vitamin B2, Vitamin B6, andVitamin C.
 19. (canceled)
 20. The nutritional composition of claim 12,further comprising at least one mineral is selected from the groupconsisting of: chromium, copper, iodine, iron, manganese, molybdenum,potassium, selenium, and sodium.
 21. The nutritional composition ofclaim 20, wherein calcium ranges from about 550 mg/20 g PE to about 840mg/20 g PE, chromium ranges from about 13.5 μg/20 g PE to about 20.9μg/20 g PE, copper ranges from about 0.15 mg/20 g PE to about 0.25 mg/20g PE, iodine ranges from about 60 μg/20 g PE to about 91.5 μg/20 g PE,iron ranges from about 6 mg/20 g PE to about 9.75 mg/20 g PE, magnesiumranges from about 125 mg/20 g PE to about 195 mg/20 g PE, manganeseranges from about 0.75 mg/20 g PE to about 1.25 mg/20 g PE, molybdenumranges from about 15 μg/20 g PE to about 25 μg/20 g PE, phosphorusranges from about 475 mg/20 g PE to about 720 mg/20 g PE, potassiumranges from about 375 mg/20 g PE to about 520 mg/20 g PE, seleniumranges from about 21 μg/20 g PE to about 32 μg/20 g PE, sodium rangesfrom about 100 mg/20 g PE to about 200 mg/20 g PE, and zinc ranges fromabout 4 mg/20 g PE to about 6 mg/20 g PE. 22-30. (canceled)